ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC.

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01774721
• Collaborator: (none)
• Enrollment: 452
• Locations: 52
• Arms: 2
• Actual Duration (Months): 104.6
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multinational, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of treatment with dacomitinib (PF-00299804) to treatment with gefitinib in patients with locally advanced or metastatic non-small cell lung cancer, with epidermal growth factor receptor EGFR-activating mutation (s). Analyses of primary objective (Progression Free Survival) will be done as defined in the protocol.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer With EGFR-Activating Mutations	Drug: Dacomitinib (PF-00299804); Drug: Gefitinib	Phase 3

Detailed Description

452 patients were randomized in a 1:1 ratio between dacomitinib (PF-00299804 ) vs. gefitinib.

Study Design

• Study Type: Interventional
• Actual Enrollment: 452 participants
• Allocation: Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ARCHER 1050: A RANDOMIZED, OPEN-LABEL, PHASE 3, EFFICACY AND SAFETY STUDY OF DACOMITINIB (PF-00299804) VERSUS GEFITINIB FOR THE FIRST LINE TREATMENT OF LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER IN SUBJECTS WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) ACTIVATING MUTATION(S)
• Actual Study Start Date: May 9, 2013
• Actual Primary Completion Date: Jul 29, 2016
• Actual Study Completion Date: Jan 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dacomitinib (PF-00299804) Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing.	Drug: Dacomitinib (PF-00299804); Dacomitinib (PF-00299804) 45 mg tablets, continuous oral daily dosing.; Other Names: Dacomitinib
Active Comparator: gefitinib Gefitinib is provided as 250 mg tablets, continuous oral daily dosing.	Drug: Gefitinib; Gefitinib 250 mg tablets, continuous oral daily dosing.; Other Names: Iressa

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)]

   PFS: time from randomization to date of progression of disease (PD) as determined by IRC review as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions (TLs), referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.

Secondary Outcome Measures

1. Progression Free Survival (PFS) Based on Investigator Assessment [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)]

   PFS: time from randomization to date of PD as determined by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD for target lesions: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm; for non-target lesions: unequivocal progression of pre-existing lesions. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.

2. Number of Participants With Best Overall Response (BOR) Based on IRC Review [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)]

   BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions;unequivocal progression of existing non TLs.

3. Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)]

   BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions;unequivocal progression of existing non TLs.

4. Objective Response Rate (ORR) Based on IRC Review [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)]

   Percentage of participants with a BOR of either CR or PR based on IRC review recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs.

5. Objective Response Rate (ORR) Based on Investigator Assessment [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)]

   Percentage of participants with a BOR of either CR or PR based on investigator assessment recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs.

6. Duration of Response (DoR) [Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)]

   DoR was defined as time from first documentation of objective response(CR or PR, whichever occurred first)to date of PD/death from any cause, whichever occurred first. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs. DoR was recorded based on IRC review and investigator's assessment and summarized for subgroup of participants with objective disease response.

7. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From baseline up to 28-35 days after last dose of study drug (up to 48 months)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non- serious adverse events.

8. Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.0: Biochemistry and Haematology [From baseline up to 28-35 days after last dose of study drug (up to 48 months)]

   Parameters included anaemia, activated partial thromboplastin time, haemoglobin, international normalized ratio, lymphocyte count, lymphopenia, neutrophils (absolute), platelets, prothrombin time and white blood cells. Biochemistry parameters included alanine aminotransferase (increased), alkaline phosphatase (increased), aspartate aminotransferase (increased), bilirubin (total), creatinine (increased), hypercalcaemia, hyperglycaemia, hyperkalaemia, hypermagnesaemia, hypernatraemia, hypoalbuminaemia, hypocalcaemia, hypoglycaemia, hypokalaemia, hypomagnesaemia, hyponatraemia. Test abnormalities were graded by AEs according to the Common Terminology Criteria for Adverse Events(NCI CTCAE) version 4.0 as Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=death related to AE. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

9. Number of Participants With Laboratory Test Abnormalities: Urinalysis [From baseline up to 28-35 days after last dose of study drug (up to 48 months)]

   Urinalysis parameter included urine protein, urine blood/haemoglobin, urine glucose and urine sediment. Test abnormalities was defined as deviation from normal range (higher or lower). Normal range of 24-hour urine protein test: less than 150 mg of protein per day, urine glucose: 0 to 0.8 mmol/L (millimole per liter), urine protein: 0 to 20 mg/dL (milligrams per deciliter). Urine blood/haemoglobin abnormality was defined as presence and absence of blood/haemoglobin in urine of participants. Urine sediment abnormality was defined as the presence of any bacteria, casts, crystals, and epithelial cells. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

10. Number of Participants With Clinically Significant Abnormalities in Vital Signs [From baseline up to 28-35 days after last dose of study drug (up to 48 months)]

    Criteria for vital signs abnormalities: systolic pulse rate less than (<) 50 beats per minute (bpm) or greater than (>)130 bpm and maximum increase or decrease from baseline in pulse rate of 30 bpm. Systolic blood pressure of maximum increase from baseline (MIB) >=40 millimeters of mercury (mmHg), maximum decrease from baseline (MDB) in systolic blood pressure =<60 mmHg. Diastolic blood pressure of MIB >=20 mmHg and MDB in diastolic blood pressure >40 and =<20 mm Hg. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

11. Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) [From baseline up to 28-35 days after last dose of study drug (up to 48 months)]

    ECG parameters included corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria for abnormality: absolute value 450 - <480 msec, 480 - <500 msec, >=500. The number of participants with potentially clinically significant ECG findings at any visit were reported.

12. Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF) [From baseline up to 7 days of Cycle 4 (up to 91 days)]

    An ejection fraction (EF) was the volumetric fraction of blood ejected from a ventricle of the heart with each heartbeat; it was a measure of the pumping efficiency of the heart. The EF of the left heart, known as the left ventricular ejection fraction, was a measure of the efficiency of pumping into the body's systemic circulation.

13. Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough [Baseline until the end of treatment (up to 48 months)]

    HRQOL was measured by standardized questionnaires (European Organization for Research and Treatment of Cancer (EORTC)) quality of life questionnaires (OLQ-C30) and its lung cancer module (QLQ-LC13). TTD in pain (chest, arm/shoulder), dyspnea, fatigue or cough was defined as time between baseline and first occurrence of increase in score of 10 points or greater from baseline in any of these 4 symptoms for at least two consecutive cycles. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment for pain, dyspnea, fatigue or cough.

14. Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS) [From Cycle 1 Day 1 up to 48 months]

    The Euro Quality of Life-5 dimension (EQ-5D) is a brief self-administered, validated reliable generic health status instrument. EQ-5D general health status can also be measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

15. Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)]

16. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose (sample collection time points had window of +/- 10% of nominal time) on Cycle 2 Day 1 (Day 29)]

17. Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)]

18. Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)]

19. Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)]

20. Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)]

    Fluctuation coefficient between trough and peak plasma concentration was determined as Cmax-Ctrough divided by Cavg, where Cmax was the maximum observed concentration within the dosing interval, Ctrough was the observed concentration prior to dose administration and Cavg was averaged plasma concentration at steady state.

21. Apparent Clearance (CL) of Dacomitinib [Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)]

    Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes).

22. Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265 [Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6]

    Trough plasma concentration was defined as the measured concentration at the end of a dosing interval at steady state (taken directly before next administration).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Evidence of histo or cytopathology confirmed, advanced NSCLC (with known histology) with the presence of EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21).

• It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon

1. to be included in this study

• No prior treatment with systemic therapy for locally advanced or metastatic NSCLC. Minimum of 12 months disease free interval between completion of neoadjuvant/adjuvant systemic therapy and recurrence of NSCLC

• Adequate tissue sample must be available for central analyses.

• Adequate renal, hematologic, liver function.

• ECOG PS of 0-1.

• Radiologically measurable disease.

Exclusion Criteria:

• Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.

• Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation.

• Any history of brain metastases or leptomeningeal metastases.

• Any previous anti-cancer systemic treatment of early, locally advanced, or metastatic NSCLC.

• Any surgery(not including minor procedures such as lymph node biopsy), palliative radiotherapy or pleurodesis within 2 weeks of baseline assessments

• Any clinically significant gastrointestinal abnormalities that may impair intake, transit or absorption of the study drug.

• Current enrollment in another therapeutic clinical study.

• History of, or currently suspected, diffuse non-infectious pneumonitis or interstitial lung disease

• Uncontrolled medical disorders.

• Prior malignancy and concurrent malignancy except for non melanoma skin cancer or in-situ cervical cancer with no evidence of active disease.

• Use of narrow therapeutic index drugs that are CYP2D6 substrates from screening to randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China
2		Changchun		China
3		Changsha		China
4		Chengdu		China
5		Chongqing		China
6		Fuzhou		China
7		Guangzhou		China
8		Hangzhou		China
9		Hefei		China
10		Nanning		China
11		Shanghai		China
12		Shenyang		China
13		Tianjin		China
14		Wuhan		China
15		Wuxi		China
16		Hong Kong		Hong Kong
17		Shatin		Hong Kong
18		Catania		Italy
19		Lecco		Italy
20		Livorno		Italy
21		Meldola		Italy
22		Milano		Italy
23		Napoli		Italy
24		Perugia		Italy
25		Ravenna		Italy
26		Roma		Italy
27		Trento		Italy
28		Viterbo		Italy
29		Hokkaido	Asahikawa	Japan
30		Kashiwa	Chiba	Japan
31		Matsuyama	Ehime	Japan
32		Yokohama	Kanagawa	Japan
33		Tokyo	Koto-ku	Japan
34		Osakasayama	Osaka	Japan
35		Sakai	Osaka	Japan
36		Sunto-gun	Shizouka	Japan
37		Chuo-Ku	Tokyo	Japan
38		Seoul		Korea, Republic of
39		Gdansk		Poland
40		Olsztyn		Poland
41		Poznan		Poland
42		Warszawa		Poland
43		Avila		Spain
44		Barcelona		Spain
45		Bilbao		Spain
46		Caceres		Spain
47		Cordoba		Spain
48		Las Palmas		Spain
49		Madrid		Spain
50		Malaga		Spain
51		San Sebastian		Spain
52		Seville		Spain

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01774721
• Other Study ID Numbers: A7471050; DP312804
• First Posted: Jan 24, 2013
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: first-line; locally advanced or metastatic; non-small cell lung cancer; epidermal growth factor receptor; EGFR; ARCHER; mutation; dacomitinib; PF-00299804
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gefitinib

Study Results

Participant Flow

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Period Title: Overall Study
STARTED	227	225
Treated	227	224
COMPLETED	0	0
NOT COMPLETED	227	225

Baseline Characteristics

Arm/Group Title	Dacomitinib	Gefitinib	Total
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Total of all reporting groups
Overall Participants	227	225	452
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (11.26)	60.9 (10.17)	61.1 (10.72)
Sex: Female, Male (Count of Participants)
Female	146 64.3%	125 55.6%	271 60%
Male	81 35.7%	100 44.4%	181 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	227 100%	225 100%	452 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	170 74.9%	176 78.2%	346 76.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.4%	0 0%	1 0.2%
White	56 24.7%	49 21.8%	105 23.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review
Description	PFS: time from randomization to date of progression of disease (PD) as determined by IRC review as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions (TLs), referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
Median (95% Confidence Interval) [months]	14.7	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	1-sided stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.589
	Confidence Interval	(2-Sided) 95%; 0.469 to 0.739
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on stratified Cox regression model

2. Secondary Outcome

Title	Progression Free Survival (PFS) Based on Investigator Assessment
Description	PFS: time from randomization to date of PD as determined by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD for target lesions: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm; for non-target lesions: unequivocal progression of pre-existing lesions. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
Median (95% Confidence Interval) [months]	16.6	11.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	1-sided stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.622
	Confidence Interval	(2-Sided) 95%; 0.497 to 0.779
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on stratified Cox regression model

3. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) Based on IRC Review
Description	BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions;unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
Complete response	12 5.3%	4 1.8%
Partial response	158 69.6%	157 69.8%
Stable disease	30 13.2%	27 12%
Progressive disease	12 5.3%	15 6.7%
Indeterminate	15 6.6%	22 9.8%

4. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment
Description	BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions;unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
Complete response	2 0.9%	1 0.4%
Partial response	169 74.4%	157 69.8%
Stable disease	38 16.7%	49 21.8%
Progressive disease	9 4%	11 4.9%
Indeterminate	9 4%	7 3.1%

5. Secondary Outcome

Title	Objective Response Rate (ORR) Based on IRC Review
Description	Percentage of participants with a BOR of either CR or PR based on IRC review recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
Number (95% Confidence Interval) [percentage of participants]	74.9 33%	71.6 31.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1942
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

6. Secondary Outcome

Title	Objective Response Rate (ORR) Based on Investigator Assessment
Description	Percentage of participants with a BOR of either CR or PR based on investigator assessment recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
Number (95% Confidence Interval) [percentage of participants]	75.3 33.2%	70.2 31.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0924
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

7. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR was defined as time from first documentation of objective response(CR or PR, whichever occurred first)to date of PD/death from any cause, whichever occurred first. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs. DoR was recorded based on IRC review and investigator's assessment and summarized for subgroup of participants with objective disease response.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	225
DoR: IRC review	14.8	8.3
DoR: Investigator assessment	15.9	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	Comparison of dacomitinib vs gefitinib based on IRC review
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	1-sided stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.403
	Confidence Interval	(2-Sided) 95%; 0.307 to 0.529
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on stratified Cox regression model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	Comparison of dacomitinib vs gefitinib based on Investigator assessment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	1-sided stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.545
	Confidence Interval	(2-Sided) 95%; 0.418 to 0.711
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on stratified Cox regression model

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non- serious adverse events.
Time Frame	From baseline up to 28-35 days after last dose of study drug (up to 48 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	224
TEAEs	226 99.6%	220 97.8%
SAEs	62 27.3%	50 22.2%

9. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.0: Biochemistry and Haematology
Description	Parameters included anaemia, activated partial thromboplastin time, haemoglobin, international normalized ratio, lymphocyte count, lymphopenia, neutrophils (absolute), platelets, prothrombin time and white blood cells. Biochemistry parameters included alanine aminotransferase (increased), alkaline phosphatase (increased), aspartate aminotransferase (increased), bilirubin (total), creatinine (increased), hypercalcaemia, hyperglycaemia, hyperkalaemia, hypermagnesaemia, hypernatraemia, hypoalbuminaemia, hypocalcaemia, hypoglycaemia, hypokalaemia, hypomagnesaemia, hyponatraemia. Test abnormalities were graded by AEs according to the Common Terminology Criteria for Adverse Events(NCI CTCAE) version 4.0 as Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=death related to AE. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
Time Frame	From baseline up to 28-35 days after last dose of study drug (up to 48 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	224
Anaemia (Grade 3)	2 0.9%	6 2.7%
Haemoglobin (Grade 3)	0 0%	1 0.4%
Lymphopenia (Grade 3)	13 5.7%	6 2.7%
Lymphopenia (Grade 4)	1 0.4%	0 0%
Neutrophil count (absolute) (Grade 3)	0 0%	1 0.4%
WBC count (Grade 3)	1 0.4%	1 0.4%
Alanine aminotransferase increased (Grade 3)	3 1.3%	26 11.6%
Alanine aminotransferase increased (Grade 4)	0 0%	2 0.9%
Aspartate aminotransferase increased (Grade 3)	1 0.4%	15 6.7%
Aspartate aminotransferase increased (Grade 4)	0 0%	2 0.9%
Alkaline phosphatase increased (Grade 3)	2 0.9%	6 2.7%
Bilirubin increased (total) (Grade 3)	1 0.4%	1 0.4%
Creatinine increased (Grade 3)	0 0%	1 0.4%
Hypercalcaemia (Grade 3)	1 0.4%	0 0%
Hyperglycaemia (Grade 3)	2 0.9%	5 2.2%
Hyperkalaemia (Grade 4)	0 0%	2 0.9%
Hypermagnesaemia (Grade 3)	7 3.1%	6 2.7%
Hypocalcaemia (Grade 3)	3 1.3%	4 1.8%
Hypoglycaemia (Grade 3)	0 0%	2 0.9%
Hypoglycaemia (Grade 4)	1 0.4%	0 0%
Hypokalaemia (Grade 3)	13 5.7%	5 2.2%
Hypokalaemia (Grade 4)	2 0.9%	0 0%
Hypomagnesaemia (Grade 3)	2 0.9%	0 0%
Hyponatraemia (Grade 3)	6 2.6%	5 2.2%
Hyponatraemia (Grade 4)	1 0.4%	1 0.4%

10. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities: Urinalysis
Description	Urinalysis parameter included urine protein, urine blood/haemoglobin, urine glucose and urine sediment. Test abnormalities was defined as deviation from normal range (higher or lower). Normal range of 24-hour urine protein test: less than 150 mg of protein per day, urine glucose: 0 to 0.8 mmol/L (millimole per liter), urine protein: 0 to 20 mg/dL (milligrams per deciliter). Urine blood/haemoglobin abnormality was defined as presence and absence of blood/haemoglobin in urine of participants. Urine sediment abnormality was defined as the presence of any bacteria, casts, crystals, and epithelial cells. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
Time Frame	From baseline up to 28-35 days after last dose of study drug (up to 48 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	224
High Urine Protein	1 0.4%	1 0.4%
Low Urine Glucose	1 0.4%	0 0%
High Urine Blood/Haemoglobin	4 1.8%	4 1.8%

11. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Vital Signs
Description	Criteria for vital signs abnormalities: systolic pulse rate less than (<) 50 beats per minute (bpm) or greater than (>)130 bpm and maximum increase or decrease from baseline in pulse rate of 30 bpm. Systolic blood pressure of maximum increase from baseline (MIB) >=40 millimeters of mercury (mmHg), maximum decrease from baseline (MDB) in systolic blood pressure =<60 mmHg. Diastolic blood pressure of MIB >=20 mmHg and MDB in diastolic blood pressure >40 and =<20 mm Hg. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
Time Frame	From baseline up to 28-35 days after last dose of study drug (up to 48 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	227	224
MIB in systolic BP >=40 mmHg	13 5.7%	20 8.9%
MDB in systolic BP <=-60 mmHg	0 0%	1 0.4%
MIB in diastolic BP >=20 mmHg	38 16.7%	44 19.6%
MDB in diastolic BP >-40 and <=-20mmHg	46 20.3%	52 23.1%
MDB in diastolic BP <=-40 mmHg	0 0%	1 0.4%
Maximum post baseline pulse rate >130 bpm	2 0.9%	2 0.9%
Minimum post baseline pulse rate <50 bpm	2 0.9%	0 0%
MIB in pulse rate >=30 bpm	13 5.7%	12 5.3%
MDB in pulse rate <=-30 bpm	17 7.5%	16 7.1%
MIB in body weight >=10%	23 10.1%	42 18.7%
MDB in body weight <=10%	45 19.8%	28 12.4%

12. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)
Description	ECG parameters included corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria for abnormality: absolute value 450 - <480 msec, 480 - <500 msec, >=500. The number of participants with potentially clinically significant ECG findings at any visit were reported.
Time Frame	From baseline up to 28-35 days after last dose of study drug (up to 48 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here, "N" (number of participants analyzed) signifies participants who were evaluable for this specified outcome measure.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	217	7
QTcF Criteria: 450-<480	5 2.2%	0 0%
QTcB Criteria: 450-<480	22 9.7%	0 0%
QTcB Criteria: 480-<500	3 1.3%	0 0%

13. Secondary Outcome

Title	Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF)
Description	An ejection fraction (EF) was the volumetric fraction of blood ejected from a ventricle of the heart with each heartbeat; it was a measure of the pumping efficiency of the heart. The EF of the left heart, known as the left ventricular ejection fraction, was a measure of the efficiency of pumping into the body's systemic circulation.
Time Frame	From baseline up to 7 days of Cycle 4 (up to 91 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here "N" signifies number of participants who were evaluable for this specified outcome measure.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	191	199
Count of Participants [Participants]	5 2.2%	5 2.2%

14. Secondary Outcome

Title	Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough
Description	HRQOL was measured by standardized questionnaires (European Organization for Research and Treatment of Cancer (EORTC)) quality of life questionnaires (OLQ-C30) and its lung cancer module (QLQ-LC13). TTD in pain (chest, arm/shoulder), dyspnea, fatigue or cough was defined as time between baseline and first occurrence of increase in score of 10 points or greater from baseline in any of these 4 symptoms for at least two consecutive cycles. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment for pain, dyspnea, fatigue or cough.
Time Frame	Baseline until the end of treatment (up to 48 months)

Outcome Measure Data

Analysis Population Description

Patient reported outcomes (PRO) analysis set included all enrolled participants, who started treatment and completed a baseline PRO assessments and at least one post-baseline PRO assessment after the first dose.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	226	222
Median (95% Confidence Interval) [months]	3.8	6.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1641
	Comments
	Method	Unstratified Log-rank Test
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.173
	Confidence Interval	(2-Sided) 95%; 0.928 to 1.483
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS)
Description	The Euro Quality of Life-5 dimension (EQ-5D) is a brief self-administered, validated reliable generic health status instrument. EQ-5D general health status can also be measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame	From Cycle 1 Day 1 up to 48 months

Outcome Measure Data

Analysis Population Description

PRO analysis set included all enrolled participants, who started treatment and completed a baseline PRO assessments and at least one post-baseline PRO assessment after the first dose. Here "N" signifies number of participants who were evaluable for this specified outcome measure.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	224	221
Mean (95% Confidence Interval) [units on a scale]	73.3869	77.6923

16. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Dacomitinib	84.19 (21.90)
PF-05199265	12.77 (7.58)

17. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose (sample collection time points had window of +/- 10% of nominal time) on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Dacomitinib	4.03
PF-05199265	6.0

18. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Dacomitinib	1712.08 (413.61)
PF-05199265	278.47 (163.53)

19. Secondary Outcome

Title	Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Dacomitinib	71.33 (17.23)
PF-05199265	11.60 (6.81)

20. Secondary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Dacomitinib	60.64 (14.85)
PF-05199265	10.49 (6.26)

21. Secondary Outcome

Title	Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265
Description	Fluctuation coefficient between trough and peak plasma concentration was determined as Cmax-Ctrough divided by Cavg, where Cmax was the maximum observed concentration within the dosing interval, Ctrough was the observed concentration prior to dose administration and Cavg was averaged plasma concentration at steady state.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Dacomitinib	0.2883 (0.1460)
PF-05199265	0.1105 (0.0827)

22. Secondary Outcome

Title	Apparent Clearance (CL) of Dacomitinib
Description	Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes).
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	19
Mean (Standard Deviation) [Liter/hour]	27.61 (5.97)

23. Secondary Outcome

Title	Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265
Description	Trough plasma concentration was defined as the measured concentration at the end of a dosing interval at steady state (taken directly before next administration).
Time Frame	Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least one measured plasma concentration and were dose-compliant. Dose-compliant participants were those who received 45 mg dacomitinib daily without interruptions or dose reductions for at least 14 days prior to the day of data collection. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points.

Arm/Group Title	Dacomitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Measure Participants	188
Cycle 2 Day 1: Dacomitinib	70.24 (27.16)
Cycle 3 Day 1: Dacomitinib	68.34 (25.80)
Cycle 4 Day 1: Dacomitinib	68.16 (25.49)
Cycle 5 Day 1: Dacomitinib	64.50 (25.52)
Cycle 6 Day 1: Dacomitinib	61.68 (22.58)
Cycle 2 Day 1: PF-05199265	13.20 (8.55)
Cycle 3 Day 1: PF-05199265	14.42 (9.10)
Cycle 4 Day 1: PF-05199265	13.70 (8.33)
Cycle 5 Day 1: PF-05199265	12.48 (6.69)
Cycle 6 Day 1: PF-05199265	13.05 (6.52)

Adverse Events

Time Frame	From baseline until 28-35 days after the last dose of study drug (up to 48 months)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study. Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
Arm/Group Title	Dacomitinib		Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.		Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
All Cause Mortality
	Dacomitinib		Gefitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/227 (33.5%)		91/224 (40.6%)
Serious Adverse Events
	Dacomitinib		Gefitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/227 (27.3%)		50/224 (22.3%)
Blood and lymphatic system disorders
Leukocytosis	1/227 (0.4%)		0/224 (0%)
Cardiac disorders
Cardiac tamponade	1/227 (0.4%)		0/224 (0%)
Arteriosclerosis coronary artery	0/227 (0%)		1/224 (0.4%)
Eye disorders
Keratitis	1/227 (0.4%)		0/224 (0%)
Gastrointestinal disorders
Diarrhoea	5/227 (2.2%)		0/224 (0%)
Abdominal pain	2/227 (0.9%)		0/224 (0%)
Abdominal distension	1/227 (0.4%)		0/224 (0%)
Gastric ulcer haemorrhage	1/227 (0.4%)		0/224 (0%)
Ileus	1/227 (0.4%)		0/224 (0%)
Mouth haemorrhage	1/227 (0.4%)		0/224 (0%)
Rectal haemorrhage	1/227 (0.4%)		0/224 (0%)
Stomatitis	1/227 (0.4%)		0/224 (0%)
Vomiting	1/227 (0.4%)		0/224 (0%)
Dyspepsia	0/227 (0%)		1/224 (0.4%)
Haematochezia	0/227 (0%)		1/224 (0.4%)
Large intestinal obstruction	0/227 (0%)		1/224 (0.4%)
General disorders
Disease progression	8/227 (3.5%)		11/224 (4.9%)
Death	1/227 (0.4%)		1/224 (0.4%)
Multiple organ dysfunction syndrome	1/227 (0.4%)		0/224 (0%)
Non-cardiac chest pain	1/227 (0.4%)		0/224 (0%)
Pyrexia	1/227 (0.4%)		0/224 (0%)
General physical health deterioration	0/227 (0%)		1/224 (0.4%)
Hepatobiliary disorders
Liver injury	2/227 (0.9%)		1/224 (0.4%)
Drug-induced liver injury	1/227 (0.4%)		1/224 (0.4%)
Bile duct stone	0/227 (0%)		1/224 (0.4%)
Cholecystitis acute	0/227 (0%)		1/224 (0.4%)
Infections and infestations
Pneumonia	5/227 (2.2%)		2/224 (0.9%)
Respiratory tract infection	2/227 (0.9%)		1/224 (0.4%)
Urinary tract infection	2/227 (0.9%)		0/224 (0%)
Bronchitis	1/227 (0.4%)		0/224 (0%)
Bronchopulmonary aspergillosis	1/227 (0.4%)		0/224 (0%)
Diverticulitis	1/227 (0.4%)		0/224 (0%)
Escherichia urinary tract infection	1/227 (0.4%)		0/224 (0%)
Gastroenteritis	1/227 (0.4%)		0/224 (0%)
Infection	1/227 (0.4%)		0/224 (0%)
Lung infection	1/227 (0.4%)		1/224 (0.4%)
Upper respiratory tract infection	1/227 (0.4%)		0/224 (0%)
Herpes zoster	0/227 (0%)		1/224 (0.4%)
Injury, poisoning and procedural complications
Facial bones fracture	1/227 (0.4%)		0/224 (0%)
Hip fracture	1/227 (0.4%)		1/224 (0.4%)
Overdose	1/227 (0.4%)		0/224 (0%)
Spinal fracture	1/227 (0.4%)		0/224 (0%)
Extradural haematoma	0/227 (0%)		1/224 (0.4%)
Subdural haematoma	0/227 (0%)		2/224 (0.9%)
Tibia fracture	0/227 (0%)		1/224 (0.4%)
Investigations
Alanine aminotransferase increased	0/227 (0%)		1/224 (0.4%)
Aspartate aminotransferase increased	0/227 (0%)		1/224 (0.4%)
Hepatic enzyme increased	0/227 (0%)		2/224 (0.9%)
Metabolism and nutrition disorders
Decreased appetite	2/227 (0.9%)		0/224 (0%)
Dehydration	1/227 (0.4%)		0/224 (0%)
Malnutrition	1/227 (0.4%)		1/224 (0.4%)
Hyponatraemia	0/227 (0%)		2/224 (0.9%)
Musculoskeletal and connective tissue disorders
Bone pain	1/227 (0.4%)		0/224 (0%)
Muscular weakness	1/227 (0.4%)		0/224 (0%)
Musculoskeletal pain	1/227 (0.4%)		0/224 (0%)
Back pain	0/227 (0%)		1/224 (0.4%)
Polymyalgia rheumatica	0/227 (0%)		1/224 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/227 (0.4%)		0/224 (0%)
Chronic myeloid leukaemia	1/227 (0.4%)		0/224 (0%)
Metastases to meninges	1/227 (0.4%)		0/224 (0%)
Malignant neoplasm progression	0/227 (0%)		1/224 (0.4%)
Pancreatic carcinoma	0/227 (0%)		1/224 (0.4%)
Nervous system disorders
Cerebral infarction	1/227 (0.4%)		2/224 (0.9%)
Cerebral venous thrombosis	1/227 (0.4%)		0/224 (0%)
Spinal cord compression	1/227 (0.4%)		0/224 (0%)
Cerebrovascular accident	0/227 (0%)		1/224 (0.4%)
Cognitive disorder	0/227 (0%)		1/224 (0.4%)
Dizziness	0/227 (0%)		1/224 (0.4%)
Post herpetic neuralgia	0/227 (0%)		1/224 (0.4%)
Psychiatric disorders
Depression	0/227 (0%)		1/224 (0.4%)
Suicide attempt	0/227 (0%)		1/224 (0.4%)
Renal and urinary disorders
Acute kidney injury	1/227 (0.4%)		0/224 (0%)
Ureterolithiasis	0/227 (0%)		1/224 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	5/227 (2.2%)		2/224 (0.9%)
Haemoptysis	2/227 (0.9%)		0/224 (0%)
Pneumonitis	2/227 (0.9%)		1/224 (0.4%)
Pneumothorax	2/227 (0.9%)		0/224 (0%)
Respiratory failure	2/227 (0.9%)		0/224 (0%)
Dyspnoea	1/227 (0.4%)		4/224 (1.8%)
Interstitial lung disease	1/227 (0.4%)		1/224 (0.4%)
Pulmonary embolism	1/227 (0.4%)		0/224 (0%)
Bronchospasm	0/227 (0%)		1/224 (0.4%)
Organizing pneumonia	0/227 (0%)		1/224 (0.4%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/227 (0.4%)		0/224 (0%)
Drug eruption	1/227 (0.4%)		0/224 (0%)
Rash maculo-papular	1/227 (0.4%)		0/224 (0%)
Decubitus ulcer	0/227 (0%)		1/224 (0.4%)
Vascular disorders
Deep vein thrombosis	1/227 (0.4%)		0/224 (0%)
Other (Not Including Serious) Adverse Events
	Dacomitinib		Gefitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	224/227 (98.7%)		217/224 (96.9%)
Blood and lymphatic system disorders
Anaemia	22/227 (9.7%)		16/224 (7.1%)
Gastrointestinal disorders
Diarrhoea	198/227 (87.2%)		125/224 (55.8%)
Stomatitis	99/227 (43.6%)		40/224 (17.9%)
Nausea	43/227 (18.9%)		49/224 (21.9%)
Constipation	30/227 (13.2%)		31/224 (13.8%)
Mouth ulceration	28/227 (12.3%)		13/224 (5.8%)
Vomiting	20/227 (8.8%)		29/224 (12.9%)
Aphthous ulcer	13/227 (5.7%)		6/224 (2.7%)
Oral pain	12/227 (5.3%)		1/224 (0.4%)
Abdominal pain	10/227 (4.4%)		12/224 (5.4%)
Dysphagia	10/227 (4.4%)		12/224 (5.4%)
Abdominal pain upper	9/227 (4%)		14/224 (6.3%)
General disorders
Asthenia	29/227 (12.8%)		28/224 (12.5%)
Chest pain	22/227 (9.7%)		32/224 (14.3%)
Fatigue	21/227 (9.3%)		19/224 (8.5%)
Mucosal inflammation	21/227 (9.3%)		8/224 (3.6%)
Pyrexia	19/227 (8.4%)		17/224 (7.6%)
Oedema peripheral	13/227 (5.7%)		7/224 (3.1%)
Pain	11/227 (4.8%)		12/224 (5.4%)
Infections and infestations
Paronychia	140/227 (61.7%)		45/224 (20.1%)
Conjunctivitis	43/227 (18.9%)		9/224 (4%)
Upper respiratory tract infection	27/227 (11.9%)		28/224 (12.5%)
Nasopharyngitis	21/227 (9.3%)		19/224 (8.5%)
Rash pustular	14/227 (6.2%)		3/224 (1.3%)
Urinary tract infection	14/227 (6.2%)		8/224 (3.6%)
Investigations
Weight decreased	58/227 (25.6%)		37/224 (16.5%)
Alanine aminotransferase increased	44/227 (19.4%)		88/224 (39.3%)
Aspartate aminotransferase increased	42/227 (18.5%)		81/224 (36.2%)
Blood bilirubin increased	20/227 (8.8%)		19/224 (8.5%)
Blood alkaline phosphatase increased	14/227 (6.2%)		7/224 (3.1%)
Gamma-glutamyltransferase increased	14/227 (6.2%)		20/224 (8.9%)
White blood cell count decreased	6/227 (2.6%)		14/224 (6.3%)
Weight increased	5/227 (2.2%)		12/224 (5.4%)
Metabolism and nutrition disorders
Decreased appetite	69/227 (30.4%)		56/224 (25%)
Hypokalaemia	22/227 (9.7%)		13/224 (5.8%)
Musculoskeletal and connective tissue disorders
Pain in extremity	31/227 (13.7%)		26/224 (11.6%)
Musculoskeletal pain	26/227 (11.5%)		28/224 (12.5%)
Back pain	18/227 (7.9%)		34/224 (15.2%)
Arthralgia	16/227 (7%)		15/224 (6.7%)
Nervous system disorders
Dysgeusia	16/227 (7%)		11/224 (4.9%)
Paraesthesia	16/227 (7%)		11/224 (4.9%)
Headache	14/227 (6.2%)		19/224 (8.5%)
Dizziness	11/227 (4.8%)		17/224 (7.6%)
Psychiatric disorders
Insomnia	24/227 (10.6%)		33/224 (14.7%)
Respiratory, thoracic and mediastinal disorders
Cough	48/227 (21.1%)		42/224 (18.8%)
Dyspnoea	29/227 (12.8%)		28/224 (12.5%)
Epistaxis	21/227 (9.3%)		5/224 (2.2%)
Nasal inflammation	15/227 (6.6%)		3/224 (1.3%)
Haemoptysis	10/227 (4.4%)		13/224 (5.8%)
Productive cough	9/227 (4%)		12/224 (5.4%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	111/227 (48.9%)		64/224 (28.6%)
Dry skin	63/227 (27.8%)		38/224 (17%)
Alopecia	53/227 (23.3%)		28/224 (12.5%)
Pruritus	45/227 (19.8%)		32/224 (14.3%)
Rash	40/227 (17.6%)		24/224 (10.7%)
Palmar-plantar erythrodysaesthesia syndrome	33/227 (14.5%)		7/224 (3.1%)
Rash maculo-papular	28/227 (12.3%)		27/224 (12.1%)
Dermatitis	25/227 (11%)		9/224 (4%)
Skin fissures	21/227 (9.3%)		6/224 (2.7%)
Acne	20/227 (8.8%)		13/224 (5.8%)
Erythema	12/227 (5.3%)		3/224 (1.3%)
Vascular disorders
Hypertension	13/227 (5.7%)		10/224 (4.5%)

Limitations/Caveats

Data for overall survival is not reported at Primary completion date and will be reported after the study completion date.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.